The pandemic created by the novel human coronavirus SARS-CoV-2 has generated many unanswered questions on the best practices for prevention and treatment for those with COVID- 19 disease. The mechanism behind the lack of apparent disease susceptibility in children is also unresolved. To answer these most critical questions, we require data on how the host immune system responds to SARS-CoV-2 infection and COVID-19 disease. Longitudinal cohorts established in naive populations are necessary for careful profiling of immune responses, disease severity, and the generation of protective memory. Disease presentation and outcome has been highly variable among age groups and those with various underlying conditions, complicating study design. Large well-characterized human cohorts are costly to initiate and difficult to develop quickly. In this study, we propose to use the DIVINCI Consortium cohorts, three geographically distinct human birth cohorts, which are already established and successfully running to be able to immediately begin sampling individuals with suspected or confirmed SARS-CoV-2 infection. Importantly, all three cohorts have the ability to collect household samples, providing insights into immunity and disease progression across a broad age range. We propose to collect respiratory samples, breast milk, stool/rectal swab, and serum/PBMC samples, and from those samples, exhaustively assay the host immune response to SARS-CoV-2. Based on the study design, we will be able to compare naive time points to those during active infection as well as samples from individuals who remained asymptomatic compared to those who develop varying degrees of symptoms. Our study proposes to comprehensively measure immune cell populations in the peripheral blood in naive (baseline) samples and convalescent samples (after infection.) We propose to develop novel reagents for measuring SARS-CoV-2-specific T and B cells. Further, we propose to measure SARS-CoV-2 viral diversity and evolution. Finally, we will be able to extensively assay serological samples to determine measurable differences in the response between individuals with mild and severe infection and asymptomatic and symptomatic infection, and track their subsequent susceptibility to re-infection. The DIVINCI consortium is uniquely situated to have immediate response to the SARS-CoV-2 pandemic with the ultimate goal of a more complete understanding of the virus and the disease.